Scar Reconstructions Research Articles

Optimal pixel signal intensity threshold for the assessment of endocardial left-ventricular scar by 3D dark blood MRI compared to bipolar voltage electro-anatomical mapping

Abstract Background Late gadolinium enhancement (LGE) MRI is considered the standard for noninvasive assessment of 3D scar architecture. Intraprocedural integration of 3D scar models improve the outcome of catheter ablation for ventricular tachycardia (VT). A pixel signal intensity (PSI) cut-off of 40 to 60% has been widely used for conventional bright-blood LGE MRI. Novel 3D MRI acquisitions with dark-blood (DB) nulling with higher spatial resolution and superior detection of (subendocardial) scar patterns are increasingly available, but the optimal pixel signal intensity (PSI) value remains unknown. Purpose To compare the accuracy of the 3D DB MRI-derived endocardial scar reconstructions at three different PSI cut-offs with endocardial electro-anatomical contact mapping in patients with scar-related VT. Methods Preprocedural 3D DB LGE MRIs were retrospectively compared to high-density endocardial left-ventricular (LV) bipolar voltage mapping (cut-off 0.5-1.5mV) obtained during endocardial mapping at sinus rhythm using the ADAS3D software. The LV scar models were aligned using the mitral valve, left ventricular apex and aorta cusps. Points with a Euclidean node-to-node distance of ≥10 mm were excluded. Variable upper PSI thresholds were set at 50%, 60% and 70%; the lower threshold at two-thirds of the upper limit. The 10% LV layer from the 3D MRI was used. The pairs of points were checked for agreement for scar or healthy (%). The Pearson correlation was used to analyze the agreement between core scar, border zone and healthy tissue area (in %) at three thresholds. Results Ten patients (90% male, mean age 65±11 year, 8 ischemic/2 nonischemic, LV ejection fraction 41±6%) were analyzed. A mean of 2024 (range 385-6810) pairs were analyzed per patient at three PSI thresholds. A correct correlation for scar or healthy was present in 67%, 69% and 69% for the upper PSI thresholds of 50%, 60% and 70% respectively. The optimal match was obtained for an upper PSI cutoff value of 70%, for healthy (r2=0.57; P=0.01), border zone (r2=0.73; P=0.01), 50% for core (r2=0.09; P=0.39). Using a 60% PSI cutoff the scar core % increased significantly compared to the 70% cutoff (12.8 ±13.8 versus 4.9±7.3, P=0.001). Conclusion The optimal depiction of the boundary between healthy and border zone scar by 3D DB MRI is best depicted at an upper PSI threshold of 70%.

Time-efficient three-dimensional transmural scar assessment provides relevant substrate characterization for ventricular tachycardia features and long-term recurrences in ischemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): - Ministerio de Ciencia e Innovación and the ProCNIC Foundation - Grant TEC2017-82408-R Background We aimed to validate a 3D methodology for transmural scar assessment using time-efficient upsampled models from 2D delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) sequences and determine the clinical implications in ischemic cardiomyopathy-related ventricular tachycardia (VT) episodes. Methods Translational study including 10 pigs with myocardial infarction and 15 patients with spontaneous VT episodes and underlying infarct-related scar. Pigs underwent 3D LGE-CMR sequences to test 3D transmural-based scar assessment using several downsampled resolutions from the original images. Validation in patients included 3D and 2D LGE-CMR studies performed within the same protocol. Transmural-based scar areas were used for correlation analyses with the cycle length (CL) of VT episodes. Scar volumes were used as a benchmark comparison. Results In pigs, 3D transmural-based scar areas showed interclass correlation coefficients >0.94 between original 3D high-resolution- and downsampled-derived models. In patients, scar area quantification in myocardial regions with 3D transmurality <0.2 (for upsampled 2D-derived models) and <0.1 (for 3D-derived models) showed direct correlation with the CL of spontaneous VT episodes (r = 0.69; p < 0.01 and r = 0.79; p < 0.01, respectively) (See Abstract Figure). After ablation, patients with VT recurrences showed lower scar areas on 3D and upsampled 2D models using <0.1 and <0.2 transmurality criteria, respectively, than patients without VT recurrences (48.5 [37.7, 67.5] vs. 91.5 [84.3, 117.3] cm2, respectively, for 3D-derived models; p = 0.004, and 64.0 [43.5, 69.5] vs. 83.0 [70.2, 99.7] cm2, respectively, for upsampled 2D models; p = 0.04). Conversely, time-consuming scar volume reconstructions from 2D or 3D LGE-CMR sequences did not show significant differences between patients with and without VT recurrences. Conclusions Three-dimensional transmural scar assessment in upsampled 2D-LGE-CMR-derived models provides time-efficient characterization of infarct-related myocardial substrates associated with the CL of spontaneous VT episodes and VT recurrences after ablation. Abstract Figure

Metabolic Scar Assessment with18F-FDG PET: Correlation to Ischemic Ventricular Tachycardia Substrate and Successful Ablation Sites.

The functional and molecular imaging characteristics of ischemic ventricular tachycardia (VT) substrate are incompletely understood. Our objective was to compare regional 18F-FDG PET tracer uptake with detailed electroanatomic maps (EAMs) in a more extensive series of postinfarction VT patients to define the metabolic properties of VT substrate and successful ablation sites. Methods: Three-dimensional (3D) metabolic left ventricular reconstructions were created from perfusion-normalized 18F-FDG PET images in consecutive patients undergoing VT ablation. PET defects were classified as severe (defined as <50% uptake) or moderate (defined as 50%-70% uptake), as referenced to the maximal 17-segment uptake. Color-coded PET scar reconstructions were coregistered with corresponding high-resolution 3D EAMs, which were classified as indicating dense scarring (defined as voltage < 0.5 mV), normal myocardium (defined as voltage > 1.5 mV), or border zones (defined as voltage of 0.5-1.5 mV). Results: All 56 patients had ischemic cardiomyopathy (ejection fraction, 29% ± 12%). Severe PET defects were larger than dense scarring, at 63.0 ± 48.4 cm2 versus 13.8 ± 33.1 cm2 (P < 0.001). Similarly, moderate/severe PET defects (≤70%) were larger than areas with abnormal voltage (≤1.5 mV) measuring 105.1 ± 67.2 cm2 versus 56.2 ± 62.6 cm2 (P < 0.001). Analysis of bipolar voltage (23,389 mapping points) showed decreased voltage among severe PET defects (n = 10,364; 0.5 ± 0.3 mV) and moderate PET defects (n = 5,243; 1.5 ± 0.9 mV, P < 0.01), with normal voltage among normal PET areas (>70% uptake) (n = 7,782, 3.2 ± 1.3 mV, P < 0.001). Eighty-eight percent of VT channel or exit sites (n = 44) were metabolically abnormal (severe PET defect, 78%; moderate PET defect, 10%), whereas 12% (n = 6) were in PET-normal areas. Metabolic channels (n = 26) existed in 45% (n = 25) of patients, with an average length and width of 17.6 ± 12.5 mm and 10.3 ± 4.2 mm, respectively. Metabolic channels were oriented predominantly in the apex or base (86%), harboring VT channel or exit sites in 31%. Metabolic rapid-transition areas (>50% change in 18F-FDG tracer uptake/15 mm) were detected in 59% of cases (n = 33), colocalizing to VT channels or exit sites (15%) or near these sites (85%, 12.8 ± 8.5 mm). Metabolism-voltage mismatches in which there was a severe PET defect but voltage indicating normal myocardium were seen in 21% of patients (n = 12), 41% of whom were harboring VT channel or exit sites. Conclusion: Abnormal 18F-FDG uptake categories could be detected using incremental 3D step-up reconstructions. They predicted decreasing bipolar voltages and VT channel or exit sites in about 90% of cases. Additionally, functional imaging allowed detection of novel molecular tissue characteristics within the ischemic VT substrate such as metabolic channels, rapid-transition areas, and metabolism-voltage mismatches demonstrating intrasubstrate heterogeneity and providing possible targets for imaging-guided ablation.

Autologous mesenchymal stem cells application in post-burn scars treatment: a preliminary study

Mesenchymal stem cells (MSCs) are multi-potent cells characterized by long term self-renewal and by potential for differentiation into cells of different mesenchymal tissue types such as fibroblasts, osteocytes, chondrocytes, and adipocytes. Their unique properties offer broad therapeutic potentials. Bone marrow has been used as the most common MSCs source, but it is gradually going to be replaced by adipose tissue which showed to contain more MSCs per unit than the bone marrow and clinical application of MSCs procured from the adipose tissue have been demonstrating at least similar results. Post-burn scars result frequently in severe both functional and aesthetic impairments in restitution and rehabilitation periods of the burn disease. Despite extensive research in the last decades, the exact mechanisms of scar formation remains unclear. The development of post-burn scars is influenced by multiple factors such as initial depth of the burn, methods of burn wound therapy, duration of the open wound until final wound closure, burn wound infection, genetic predisposition, and many others in both acute and rehabilitation periods. The aim of this study was to point out versatility of the implementation of this method with respect to different types of scars (atrophic scars, hypertrophic scars, keloids). Autologous adipose tissue derived MSCs were applied to post-burn scars in all 8 patients undergoing surgical scar reconstructions at the Department of Burns and Reconstructive Surgery of the University Hospital in Bratislava. The study was approved by Ethical Committee of Ruzinov Hospital. The procedures used for scar reconstructions included dermabrasion, scar excisions, contractures corrections and local plasties combined by lipografting of lipoaspirate containing parenchymal adipocytes and stromal vascular fraction including MSCs, or application of separated autologous MSCs isolated from lipoaspirates. Based on desired result one of these MSCs application methods was selected depending on characteristics of reconstructed scar and required volume of transferred fat. Isolation of MSCs following procurement was provided by the Central Tissue Bank cell culture laboratory which is one of the parts of the burn department. The average time of scars duration was 79months, ranging from 6 to 216months. The postburns scars were assessed clinically according to Vancouver Scar Scale (VSS) prior to surgery, including photo documentation, and re-evaluated after 6months following MSCs application. As the results have shown, the average VSS score before treatment was 7.88 points ranging from 4 to 11 points. The average VSS 6months after surgical procedure and MSCs application was 2.34 points ranging from 1 to 4 points. According to the results obtained, the favourable effect of adipose tissue derived autologous MSCs application on scar remodelling following surgical reconstruction of post-burn scars could be promising.

Widespread fire years in the US–Mexico Sky Islands are contingent on both winter and monsoon precipitation

The climate of the south-western United States and northern Mexico borderlands is marked by a bimodal precipitation regime with the majority of moisture arriving during the cool season via Pacific frontal storm systems, and intense convective storms during the North American Monsoon (NAM). The fire season occurs primarily during the arid foresummer in May and June, before the development of the NAM. Most tree-ring studies of fire climatology in the region have evaluated only the role of winter precipitation. We used tree-ring-width-based reconstructions of both winter and monsoon precipitation, coupled with fire scar reconstructions of fire history from mountain ranges in the US and Mexico, to quantify the historical role and interactions of both seasons of precipitation in modulating widespread fire years. Winter precipitation was the primary driver of widespread fire years in the region, but years with drought in both seasons had the highest fire frequency and most widespread fires. These relationships define a unique monsoon fire regime, in which the timing and amount of monsoon precipitation are important factors in limiting the length of fire season and regulating widespread fire years.

Three-dimensional cardiac fibre disorganization as a novel parameter for ventricular arrhythmia stratification after myocardial infarction.

AimsMyocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI.Methods and resultsTwelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36–0.37 vs. 0.32; 0.26–0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320).ConclusionThe amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI.

CMR–Based Identification of Critical Isthmus Sites of Ischemic and Nonischemic Ventricular Tachycardia

ObjectivesThis study evaluates whether contrast-enhanced (CE) cardiac magnetic resonance (CMR) can be used to identify critical isthmus sites for ventricular tachycardia (VT) in ischemic and nonischemic heart disease. BackgroundFibrosis interspersed with viable myocytes may cause re-entrant VT. CE-CMR has the ability to accurately delineate fibrosis. MethodsPatients who underwent VT ablation with CE-CMR integration were included. After the procedure, critical isthmus sites (defined as sites with a ≥11 of 12 pacemap, concealed entrainment, or VT termination during ablation) were projected on CMR-derived 3-dimensional (3D) scar reconstructions. The scar transmurality and signal intensity at all critical isthmus, central isthmus, and exit sites were compared to the average of the entire scar. The distance to >75% transmural scar and to the core-border zone (BZ) transition was calculated. The area within 5 mm of both >75% transmural scar and the core-BZ transition was calculated. ResultsIn 44 patients (23 ischemic and 21 nonischemic, left ventricular ejection fraction 44 ± 12%), a total of 110 VTs were induced (cycle length 290 ± 67 ms). Critical isthmus sites were identified for 78 VTs (71%) based on ≥11 of 12 pacemaps (67 VTs), concealed entrainment (10 VTs), and/or termination (30 VTs). The critical isthmus sites, and in particular central isthmus sites, had high scar transmurality and signal intensity compared with the average of the entire scar. Of the pacemap, concealed entrainment, and termination sites, 74%, 100%, and 84% were within 5 mm of >75% transmural scar, and 67%, 100%, and 94% were within 5 mm of the core-BZ transition, respectively. The areas within 5 mm of both >75% transmural scar and the core-BZ transition (median 13% of LV) contained all concealed entrainment sites and 77% of termination sites. ConclusionsBoth in ischemic and nonischemic VT, critical isthmus sites are typically located in close proximity to the CMR-derived core-BZ transition and to >75% transmural scar. These findings suggest that CMR-derived scar characteristics may guide to critical isthmus sites during VT ablation.

Contrast-Enhanced MRI–Derived Scar Patterns and Associated Ventricular Tachycardias in Nonischemic Cardiomyopathy

Background— There are limited data on typical arrhythmogenic substrates and associated ventricular tachycardias (VT) in patients with nonischemic cardiomyopathy. The substrate location may have implications for the ablation strategy. Methods and Results— Nineteen consecutive patients with nonischemic cardiomyopathy (age 58±14 years, 79% men, left ventricular ejection fraction 41±11%) who underwent contrast-enhanced MRI and VT ablation were included. On the basis of 3-dimensional contrast-enhanced MRI–derived scar reconstructions, 8 patients (42%) had predominant basal anteroseptal scar, 9 patients (47%) had predominant inferolateral scar, and 2 patients (11%) had other scar types. Three distinct VT morphologies (≥1 of 3 inducible in 16/19 patients) were associated with underlying scar type. In 9 patients with anteroseptal scar–related VT (8/9 predominant scar, 1/9 nonpredominant), ablation target sites (defined as sites with ≥11/12 pacemap, concealed entrainment or VT termination during ablation) were located in the aortic root and/or anteroseptal left ventricular endocardium in 8 patients (89%) and in the anterior cardiac vein in 1 patient (11%), with additional target sites at the right ventricular septum in 2 patients (22%) and at the epicardium in 1 patient (11%). In contrast, in 8 patients with predominant inferolateral scar–related VT, target sites were located at the epicardium in 5 patients (63%) and in the endocardial inferolateral left ventricle in 3 patients (37%). Conclusions— Two typical scar patterns (anteroseptal and inferolateral) account for 89% of arrhythmogenic substrates in patients with nonischemic cardiomyopathy. Three distinct VT morphologies are highly suggestive of the presence of these scars. Anteroseptal scars were, in general, most effectively approached from the aortic root or anteroseptal left ventricular endocardium, whereas inferolateral scars frequently required an epicardial approach.

Integration of 3D Electroanatomic Maps and Magnetic Resonance Scar Characterization Into the Navigation System to Guide Ventricular Tachycardia Ablation

Scar heterogeneity identified with contrast-enhanced cardiac magnetic resonance (CE-CMR) has been related to its arrhythmogenic potential by using different algorithms. The purpose of the study was to identify the algorithm that best fits with the electroanatomic voltage maps (EAM) to guide ventricular tachycardia (VT) ablation. Three-dimensional scar reconstructions from preprocedural CE-CMR study at 3T were obtained and compared with EAMs of 10 ischemic patients submitted for a VT ablation. Three-dimensional scar reconstructions were created for the core (3D-CORE) and border zone (3D-BZ), applying cutoff values of 50%, 60%, and 70% of the maximum pixel signal intensity to discriminate between core and BZ. The left ventricular cavity from CE-CMR (3D-LV) was merged with the EAM, and the 3D-CORE and 3D-BZ were compared with the corresponding EAM areas defined with standard cutoff voltage values. The best match was obtained when a cutoff value of 60% of the maximum pixel signal intensity was used, both for core (r(2)=0.827; P<0.001) and BZ (r(2)=0.511; P=0.020), identifying 69% of conducting channels (CC) observed in the EAM. Matching improved when only the subendocardial half of the wall was segmented (CORE: r(2)=0.808; P<0.001 and BZ: r(2)=0.485; P=0.025), identifying 81% of CC. When comparing the location of each bipolar voltage intracardiac electrogram with respect to the 3D CE-CMR-derived structures, a Cohen κ coefficient of 0.70 was obtained. Scar characterization by means of high resolution CE-CMR resembles that of EAM and can be integrated into the CARTO system to guide VT ablation.

Efficacy of Skin Stretching for Burn Scar Excision: A Multicenter Randomized Controlled Trial

Burn survivors are frequently faced with disfiguring scars. Various techniques exist to improve scar appearance, such as laser treatment and dermabrasion. Next to that, surgical reconstruction, such as scar excision is an option. This randomized controlled trial investigates whether a larger burn scar can be excised using a skin-stretching device for wound closure, thereby optimizing use of adjacent healthy skin. This technique may allow scar excision in a one-step procedure instead of two or more steps, which is necessary for serial excision and tissue expansion. Two arms were compared: scar excision and closure by skin stretch and scar excision without additional techniques. The primary outcome measure was scar surface area reduction. In addition, complications were registered. Fifteen patients were randomized for skin stretch and 15 patients were randomized for scar excision only. In the skin stretch group, 10 of 15 scars were completely excised compared with three of 15 in the scar excision-only group (p = 0.025). In the skin stretch group, a significantly larger reduction in scar area was achieved: 95 ± 11 percent of the scar was excised versus 78 ± 17 percent in the scar excision-only group (p = 0.003). One patient in the skin stretch group and three patients in the scar excision-only group experienced partial wound dehiscence (p = 0.598). In burn scar reconstructions, a significantly larger reduction in scar area can be achieved using a skin-stretching device compared with scar excision with no additional techniques, without an increased risk of complications. It was shown that skin stretching is of added value for scars that cannot be excised in a one-step procedure.

Three-Dimensional Contrast-Enhanced Multidetector CT for Anatomic, Dynamic, and Perfusion Characterization of Abnormal Myocardium To Guide Ventricular Tachycardia Ablations

Background— Advances in contrast-enhanced multidetector CT enable detailed characterization of the left ventricular myocardium. Myocardial scar and border zone (BZ), as the target of ventricular tachycardia ablations, displays abnormal anatomic, dynamic, and perfusion characteristics during first-pass CT. This study assessed how contrast-enhanced CT can predict voltage-defined scar and BZ and integrate its scar reconstructions into clinical mapping systems to guide ventricular tachycardia ablations. Methods and Results— Eleven patients with ischemic cardiomyopathy underwent contrast-enhanced CT before ventricular tachycardia ablation. Segmental anatomic (end-systolic and end-diastolic wall thickness), dynamic (wall thickening, wall motion), and perfusion (hypoenhancement) characteristics were evaluated. Receiver operating characteristic curves assessed the ability of CT to determine voltage-defined scar and BZ segments. Three-dimensional epi- and endocardial surfaces and scar borders were reconstructed, coregistered, and compared to voltages using a 17-segment model. Abnormal anatomic, dynamic, and perfusion data correlated well with abnormal (&lt;1.5 mV) endocardial voltages ( r =0.77). Three-dimensional reconstruction integrated into the clinical mapping system (registration accuracy, 3.31±0.52 mm) allowed prediction of homogenous abnormal voltage (&lt;1.5 mV) in 81.7% of analyzed segments and correctly displayed transmural extent and intramural scar location. CT hypoperfusion correlated best with scar and BZ areas and encompassed curative ablations in 82% cases. Conclusions— Anatomic, dynamic, and perfusion imaging using contrast-enhanced CT allows characterization of left ventricular anatomy and 3D scar and BZ substrate. Integration of reconstructed 3D data sets into clinical mapping systems supplements information of voltage mapping and may enable new image approaches for substrate-guided ventricular tachycardia ablation.

Clinical Application of PET/CT Fusion Imaging for Three‐Dimensional Myocardial Scar and Left Ventricular Anatomy during Ventricular Tachycardia Ablation

Integration of 3D PET with Voltage Map for VT Ablation. Background: Image integration has the potential to display three-dimensional (3D) scar anatomy and facilitate substrate characterization for ventricular tachycardia (VT) ablation. However, the current generation of clinical mapping systems cannot display 3D left ventricle (LV) anatomy with embedded 3D scar reconstructions or allow display of border zone and high-resolution anatomic scar features. Objective: This study reports the first clinical experience with a mapping system allowing an integrated display of 3D LV anatomy with detailed 2D/3D scar and border zone reconstruction. Methods: Ten patients scheduled for VT ablation underwent contrast-enhanced computed tomography (CT) and Rubidium-82 perfusion/F-18 Fluorodeoxyglucose metabolic Positron Emission Tomography (PET) imaging to reconstruct 3D LV and scar anatomy. LV and scar models were co-registered using a 3D mapping system and analyzed with a 17-segment model. Metabolic thresholding was used to reconstruct the 3D border zone. Real-time display of CT images was performed during ablation. Results: Co-registration (error 4.3 +/- 0.7 mm) allowed simultaneous visualization of 3D LV anatomy and embedded scar and guided additional voltage mapping. Segments containing homogenous or partial scar correlated in 94.4% and 85.7% between voltage maps and 3D PET scar reconstructions, respectively. Voltage-defined scar and normal myocardium had relative FDG uptakes of 40 +/- 13% and 89 +/- 30% (P < 0.05). The 3D border zone correlated best with a 46% metabolic threshold. Real-time display of registered high-resolution CT images allowed the simultaneous characterization of scar-related anatomic changes. Conclusion: Integration of PET/CT reconstruction allows simultaneous 3D display of myocardial scar and border zone embedded into the LV anatomy as well as the display of detailed scar anatomy. Multimodality imaging may enable a new image-guided approach to substrate-guided VT ablation.

The Role of Fibroblasts in Skin Substitutes

Skin substitutes are slowly finding a position in the treatment of burns, scar reconstructions and chronic wounds. Some of the substitutes consist of extracellular matrix replacement material only, such as Integra and Alloderm; some include allogeneic cells (Dermagraft, Appligraf). The ideal skin substitute has not been developed yet, since none of the presently available products can ultimately prevent scar formation.Study of the role of autologous fibroblasts in the healing process might give further insight into the scarring process and eventually lead to improved skin substitutes.We compared wound reepithelialization of experimental wounds treated with proliferating keratinocytes and a dermal substitute with either dermal fibroblasts, adipose tissue derived fibroblasts or no fibroblasts. We also investigated the rate of keratinocyte migration of human skin equivalents cultured in vitro in the presence of dermal or adipose tissue derived fibroblasts.We reached successful wound closure in 8 days with transfer of proliferating keratinocytes on a dermal substitute seeded with dermal fibroblasts. However, the wounds treated with substitutes which contained adipose tissue derived fibroblasts or no fibroblasts at all were not closed even after 21 days.Keratinocytes seeded onto collagen lattices populated with either dermal or fat‐derived fibroblasts showed similar findings: a retarded migration and/or proliferation of keratinocytes on the collagen lattices with fat‐derived fibroblasts. The collagen lattices populated with fat‐derived fibroblasts also showed a marked contraction, up till 50% of the original area.In both models, more alpha‐smooth muscle actin positive cells were found in the fibroblast population from adipose origin.We conclude that epidermal regeneration is negatively influenced by the presence of fat‐derived fibroblasts in a dermal matrix; possibly, myofibroblasts play a role in this.

Long-term results of a clinical trial on dermal substitution.: A light microscopy and Fourier analysis based evaluation

Although dermal substitution is a main topic of current wound healing research, there is a paucity of clinical trials with a long-term clinical and histopathological evaluation. A clinical trial was conducted to perform an intra-individual comparison of conventional treatment (split-thickness autograft) to a collagen/elastin dermal substitute in combination with an autograft. Promising results with this substitute were obtained with respect to dermal organisation and scar elasticity in animal studies and clinical trials with a short-term follow-up. Twenty-nine of the 42 pairs of the burn wounds and 28 of the 44 pairs of the scar reconstructions enrolled in the study were biopsied after 1 year. Promising but not statistically significant differences were found between substituted groups and control groups for epidermal thickness, basement membrane maturation, rete ridges ( P=0.055), fibroblasts, myofibroblasts, inflammatory cells, vessels and extracellular matrix maturation. An objective and accurate technique, Fourier analysis, was used to evaluate collagen bundle orientation and packing. However, no statistically significant differences were obtained for these parameters. This microscopic evaluation provided no convincing evidence for a long-term effectiveness of a dermal substitute despite promising data over a short-term in in vitro and in vivo studies with the same material.